Rosiglitazone suppresses gastric carcinogenesis by up-regulating HCaRG expression.
Our previous study demonstrated that PPARgamma ligand rosiglitazone prevents gastric carcinogenesis in rats induced by chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In this study, we attempted to identify novel anti-cancer mechanisms of rosiglitazone. By examining the gene expression profiles of MNNG-induced and rosiglitazone-treated gastric cancer with Uniset Rat I Bioarray microarray, we identified a gene that showed prominent responses in the rosiglitazone-treated group. The hypertension-related, calcium-regulated gene (HCaRG) was significantly up-regulated in rat gastric carcinoma of the rosiglitazone-treated group when compared with the MNNG group. We further examined HCaRG expression in human gastric cancer and found that the expression of HCaRG was down-regulated in human gastric cancerous tissue. Rosiglitazone markedly induced the expression of HCaRG in the AGS cell line. The up-regulation of HCaRG may be one of the mechanisms underlying the chemopreventive effect of rosiglitazone in gastric cancer.
Chen
Bai-Li
BL
Department of Gastroenterology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China.
Yu
Jun
J
Zeng
Zhi-Rong
ZR
Chu
Wai-Kit
WK
Wong
Christine Y P
CY
Cheng
Yuen-Yee
YY
Sung
Joseph J Y
JJ
Hu
Pin-Jin
PJ
Leung
Wai K
WK
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*; D015854:Up-Regulation
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C415469:Commd5 protein, rat; D009687:Nuclear Proteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008769:Methylnitronitrosoguanidine